Conventionally, in the case of conducting a series of reaction treatments using a large number of reagents or substances for a target material which is an object to be examined, for example, the target material is bonded to a minute carrier made of beads or the like and then the resultant is incorporated into a test tube. Thereafter, various ones of the reagents or substances are injected to the test tube to separate the carrier in some manner. The carrier is then moved to a different container, and further different ones of the reagents or substances are injected thereto or are subjected to heating treatment or some other treatment. In a case where the carrier is, for example, a magnetic substance, the separation is attained by causing the carrier to be adsorbed onto the inner wall of the test tube by a magnetic field.
About the processing of using a planar carrier, such as a prepared slide, to which, for example, various oligonucleotides are fixed to examine a target material, the base sequence structure of the target material is examined by conducting a series of reaction treatments, such as a treatment of moving the carrier itself into a suspension wherein the target material that has been marked is suspended, a treatment of partitioning various reagents into the carrier itself, a treatment of moving the carrier itself into a washing solution, and a treatment of moving the carrier to a measuring position of a measuring device in order to measure light emitted therefrom.
In order to conduct these treatments, it is necessary to separate the carrier itself and move the carrier itself. Thus, there remain problems that the treatments are complicated and require much time and labor. In particular, in the case of moving such carriers themselves, much burden is imposed to users when the movement is manually attained. Moreover, cross-contamination may be caused. In the case of moving the carriers themselves mechanically, a large-scaled apparatus is necessary. In the case of separating the carrier of a nonmagnetic type, there is a problem that the separation needs to be attained by aid of the size or specific gravity of the carrier so that the treatment is complicated and requires much time and labor.
Thus, an apparatus using a partitioning device invented by the present inventors without using any test tube or planar carrier is known, the apparatus having a pipette chip having a liquid-passing path through which liquid can pass, a nozzle to which the pipette chip is fitted, a magnetizing device for applying a magnetic field to the liquid-passing path of the pipette chip, and a sucking and discharging mechanism including a cylinder having therein a plunger for sucking and discharging a fluid into/from the pipette chip.
According to this method, a suspension wherein many magnetic particles having surfaces which hold various substances are suspended is sucked, and a magnetic field is applied thereto at the time of the suction, whereby the magnetic particles are effectively caused to be adsorbed to the liquid-passing path of the pipette chip, so as to attain separation thereof or the like. However, the magnetic particles can pass through the liquid-passing path; it is therefore necessary to apply a magnetic field to the magnetic particles so as to cause the particles to be adsorbed on the inner wall in order that the pipette chip can hold therein the magnetic particles. It is therefore necessary to combine the control of suction and discharge, the control of adsorption through the magnetic field, and the moving control of the pipette chip with each other in order to conduct the processing. In a case where the carrier is made of nonmagnetic particles, there also remains a problem that the carrier cannot be separated by means of the apparatus.
Furthermore, the cylinder for driving the plunger is used as the sucking and discharging mechanism, and the plunger or some other similar mechanism is a highly-precise worked member such as a syringe. In particular, the volume change of the inside of the cylinder unifies basically with the volume change of the inside of the partitioning chip; thus, it is necessary to transmit the change so as not to loosen a jointing region between the plunger and the driving device for the plunger. It is also necessary to fit the nozzle of the sucking and discharging mechanism to the partitioning chip or the like without leaking off air or liquid. Thus, precision and structure for attaining watertightness or airtightness are required for production or quality-control. In particular, in a case where plural partitioning chips are integrated with each other and used, a large force is required for inserting and fitting plural nozzles into the portioning chips simultaneously so as to be set thereto. As a result, O rings, which are members for keeping watertightness and airtightness, may be severely worn away. Thus, a high-level quality control may be required.
In the case of fitting plural partitioning chips to nozzles of the sucking and discharging mechanism while exchanging the chips, so as to conduct treatments continuously, it is necessary to prevent cross-contamination by the contact between the nozzles and gas or liquid in the partitioning chips.
Furthermore, in order to control the suction and the discharge of the partitioning chips, cylinders having a volume consistent with the volume of the partitioning chips are required; thus, in order to handle a liquid having a large volume, there arises a problem that the scale of the apparatus becomes large (Patent Documents 1 to 3).
Known is also a method of holding beads with probes in small holes and then moving the beads into a capillary or groove to arrange the beads in a predetermined order in accordance with the kinds of the beads to produce a probe bead array, or causing beads with probes to flow in a liquid flow in a predetermined order and then putting the beads into a groove or capillary to produce a probe array having array pieces arranged in a predetermined order (Patent Document 4).
Furthermore, as a system or method for detecting many substances to be analyzed in a fluid sample, and analyzing the substances at real time to display the results, known is a system or method having at least one light source, at least one photodetector, optical assemblies on substantially the same plane, and a memory medium that can communicate with a computer, can be read by the computer and can store commands from the computer, wherein one of the commands includes a treatment of some biological sample, using a flow cytometer, and a decision of the existence and the amount of at least one interested substance to be analyzed in the biological sample, the treatment and the decision being simultaneously conducted (Patent Document 5).
However, particles are very small (for example, from several tens of micrometers to several millimeters) for being handled by persons; therefore, there is a problem that in order to arrange many particles in a predetermined order into a groove or capillary precisely, much labor and time are necessary, and the operation for the arrangement is difficult. There is also a problem that the arrangement of the particles gets out of position so that the particles cannot be matched with precise positions. Additionally, in the case of using the flow cytometer to move particles suspended in a liquid at a high speed and measuring the particles with the photodetector, it is necessary to trace the particles one by one strictly, and measure the particles. Thus, there remains a problem that the structure of the apparatus may become complicated or complicated control may become necessary.
[Patent Document 1] Japanese Patent No. 3115501
[Patent Document 2] Internal Publication WO 96/29602
[Patent Document 3] Internal Publication WO 97/44671
[Patent Document 4] Japanese Patent Application Laid-Open (JP-A) No. 2000-346842
[Patent Document 5] Japanese Patent Application National Publication No. 14-534657